In a rodent bioassay conducted by the National Toxicology Program, di(2-ethyl-hexyl)phthalate (DEHP) was found to be carcinogenic for the liver in B6C3F1 mice and F344 rats. Since DEHP also causes peroxisome proliferation, it has been suggested that the carcinogenicity of this chemical may be related to excessive peroxisomal production of H202. It is the objective of this project to examine the changes in H202 production from peroxisomal fatty acyl-CoA oxidation in livers of rats and mice treated with DEHP. Further assessment of an involvement of reactive intermediates of oxygen reduction in DEHP induced hepatotoxicity will be made from measurements of (a) activities of enzymes that eliminate toxic oxygen products (catalase, superoxide dismutase, glutathione peroxidase), (b) lipid peroxidation, and (c) superoxide anion radical production.